transplantation Flashcards
rejection
damage done by immune system to a transplanted organ
autologous transplant
tissue returning to same individual after a period outside body, usually in frozen state
syngeneic transplant
transplant between identical twins
also called isograft
allogeneic transplant
takes place between genetically non-identical members of same species
always risk rejection
cadaveric transplantation
use organs from dead donor
xenogeneic transplant
between different species
highest risk rejection
criteria for solid organ transplantation
good evidence damage is irreversible
alternative treatments not applicable
disease must not reccur
minimising chance of rejection
donor + recipient ABO compatible
recipient must not have anti-donorHLA anitbodies
donor close as poss HLA match to recipient
immunosuppression therapy
complications of transplantation
graft rejection graft vs host disease infection neoplasm drug side effects disease recurrence
is immunosuppresion required for cornea transplant
no - doesnt become vascularised
hyperacute rejection
within mins/hrs
preformed antibodies to ABO/HLA
antibody binding triggers TII H.S
graft destroyed by vascular thrombosis
preventing hyperacute rejection
careful ABO and HLA crossmatching
acute rejection
within days/weeks
TIV H.S
donor dendritic cells stimulate allogenic response in local lymph node - T cells proliferate and migrate to graft
HLA incompatibility main cause
acute rejection vs accelerated rejection
accelerated: 2-5days, pre-sensitised T cells
acute: 7-21days, newly sensitised T cells
immunology of graft rejection
afferent phase: donor MHC molecules on dendritic cells within graft recognised by CD4+ T cells (allorecognition)
efferent phase: CD4+ T cells recruit effector cells: macrophages, CD8+ T cells, B lymphocytes, NK cells
chronic rejection
months-years
element of allogenic reaction often mediated by T cells (can result in repeated acute infection)
may be caused by recurrence of pre-existing autoimmune disease
tolerance and transplantation
no response to alloantigens on transplanted tissue but response to pathogens is not affected
tissue typing techniques
HLA typing
HLA cross matching
HLA cross matching
B cells from donor blood (chosen as express HLA class I and II) mixed with recipient serum
ensures recipient has not made any antibodies to donor antigens
SCT
heamapoeitic stem cells used to restore myeloid and lymphoid cells
autologous SCT
marrow removed, frozen and reinfused after chemotherapy
minimual immunologic risk
alllogenic SCT
very high risk
indications
- haematological malignancy with no other Rx options
- 1ry immunodeficiency e.g. SCID
- where myeloid cell production is reduced/notably abnormal cells e.g. aplastic anaeima
stem cell sources
bone marrow: aspirated with donor under GA
peripheral blood: donor treated with colony-stimulating factors to inc number circulating stem cells
cord blood: immature lymphocytes less likely to cause reaction
SCT conditioning
high dose chemotherpay
high dose radiotherapy
destroy recipient stem cells and allow engraftment of donor cells
problems with xenotransplantation
- non-primate species have gal-a1,3-gal sugar side chains which all humans have antibodies against –> hyperacute rection
- xenotransplant organs activate recipient complement
